Angiopoietin-like 4 Modifies the Interactions between Lipoprotein Lipase and Its Endothelial Cell Transporter GPIHBP1.

The release of fatty acids from plasma triglycerides for tissue uptake is critically dependent on the enzyme lipoprotein lipase (LPL). Hydrolysis of plasma triglycerides by LPL can be disrupted by the protein angiopoietin-like 4 (ANGPTL4), and ANGPTL4 has been shown to inactivate LPL in vitro. However, in vivo LPL is often complexed to glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1) on the surface of capillary endothelial cells. GPIHBP1 is responsible for trafficking LPL across capillary endothelial cells and anchors LPL to the capillary wall during lipolysis. How ANGPTL4 interacts with LPL in this context is not known. In this study, we investigated the interactions of ANGPTL4 with LPL-GPIHBP1 complexes on the surface of endothelial cells. We show that ANGPTL4 was capable of binding and inactivating LPL complexed to GPIHBP1 on the surface of endothelial cells. Once inactivated, LPL dissociated from GPIHBP1. We also show that ANGPTL4-inactivated LPL was incapable of binding GPIHBP1. ANGPTL4 was capable of binding, but not inactivating, LPL at 4 °C, suggesting that binding alone was not sufficient for ANGPTL4's inhibitory activity. We observed that although the N-terminal coiled-coil domain of ANGPTL4 by itself and full-length ANGPTL4 both bound with similar affinities to LPL, the N-terminal fragment was more potent in inactivating both free and GPIHBP1-bound LPL. These results led us to conclude that ANGPTL4 can both bind and inactivate LPL complexed to GPIHBP1 and that inactivation of LPL by ANGPTL4 greatly reduces the affinity of LPL for GPIHBP1.

Post-hatch heat warms adult beaks: irreversible physiological plasticity in Japanese quail.

Across taxa, the early rearing environment contributes to adult morphological and physiological variation. For example, in birds, environmental temperature plays a key role in shaping bill size and clinal trends across latitudinal/thermal gradients. Such patterns support the role of the bill as a thermal window and in thermal balance. It remains unknown whether bill size and thermal function are reversibly plastic. We raised Japanese quail in warm (30°C) or cold (15°C) environments and then at a common intermediate temperature. We predicted that birds raised in cold temperatures would develop smaller bills than warm-reared individuals, and that regulation of blood flow to the bill in response to changing temperatures would parallel the bill's role in thermal balance. Cold-reared birds developed shorter bills, although bill size exhibited 'catch-up' growth once adults were placed at a common temperature. Despite having lived in a common thermal environment as adults, individuals that were initially reared in the warmth had higher bill surface temperatures than cold-reared individuals, particularly under cold conditions. This suggests that blood vessel density and/or the control over blood flow in the bill retained a memory of early thermal ontogeny. We conclude that post-hatch temperature reversibly affects adult bill morphology but irreversibly influences the thermal physiological role of bills and may play an underappreciated role in avian energetics.

Is there a role for clinical practice guidelines in multidisciplinary tumor board meetings? A descriptive study of knowledge transfer between research and practice.

The aim of this study was to characterize practice patterns and decision-making processes of healthcare providers attending weekly neuro-oncology tumor board meetings, and to assess their familiarity with clinical practice guidelines (CPGs) in neuro-oncology. Members of the Neuro-Oncology Tumor Team at two tertiary cancer centers completed a web-based questionnaire assessing characteristics of weekly tumor board meetings and perceptions of CPGs. Twenty-three (66%) tumor team members responded. Diagnostic imaging results and interpretation, medical, surgical, and/or radiation treatment planning, and pathology results and interpretation were the most commonly identified aspects of patient care discussed at tumor board meetings, and almost all respondents indicated that these meetings were "very beneficial" to their own practice. When deciding on a treatment plan, respondents rely most on the clinical expertise of colleagues, medical literature, personal experience, active clinical trial protocols, and published CPGs. Opinions of the local CPGs varied considerably, and while 56% of respondents supported regular discussion of them during meetings, only 32% indicated that they were routinely reviewed. Updating the literature more frequently, implementing a formal grading system for the evidence, and incorporating clinical care pathways were the most frequently cited methods to improve the CPGs. Tumor board meetings are beneficial to the treatment planning process for neuro-oncology patients.